Cut homeodomain transcription factor is a novel regulator of growth and morphogenesis of cortex glia niche around neural cells.

Cortex glia in Drosophila central nervous system form a niche around neural cells for necessary signals to establish cross talk with their surroundings. These cells grow and expand their thin processes around neural cell bodies. Although essential for the development and function of the nervous system, how these cells make extensive and intricate connected networks remains largely unknown. In this study, we show that Cut, a homeodomain transcription factor, directly regulates the fate of the cortex glia, impacting neural stem cell (NSC) homeostasis. Focusing on the thoracic ventral nerve cord, we found that Cut is required for the normal growth and development of cortex glia and timely increase in DNA content through endocycle to later divide via acytokinetic mitosis. Knockdown of Cut in cortex glia significantly reduces the growth of cellular processes, the network around NSCs, and their progeny's cell bodies. Conversely, overexpression of Cut induces overall growth of the main processes at the expense of side ones. Whereas the Cut knockdown slows down the timely increase of DNA, the Cut overexpression results in a significant increase in nuclear size and volume and a 3-fold increase in DNA content of cortex glia. Further, we note that constitutively high Cut also interfered with nuclei separation during acytokinetic mitosis. Since the cortex glia form syncytial networks around neural cells, the finding identifies Cut as a novel regulator of glial growth and variant cell cycles to support a functional nervous system.

Guidance for the use and interpretation of assays for monitoring anti-genotoxicity.

Since DNA damage can occur spontaneously or be produced by the environmental genotoxins in living cells, it is important to investigate compounds that can reverse or protect DNA damage. An appropriate methodology is essential for the responsive identification of protection offered against DNA damage. This review includes information on the current state of knowledge on prokaryotic cell-based assays (SOS chromotest, umu test, vitotox assay) and cytogenetic techniques (micronucleus assay, chromosome aberration test and sister chromatid exchange assay) with an emphasis on the possibility to explore genoprotective compounds. Throughout the last decade, studies have extrapolated the scientific methodologies utilized for genotoxicity to assess genoprotective compounds. Therefore, shortcomings of genotoxicity studies are also mirrored in antigenotoxicity studies. While regulatory authorities around the world (OECD, US-EPA and ICH) continue to update diverse genotoxic assay strategies, there are still no clear guidelines/approaches for efficient experimental design to screen genoprotective compounds. As a consequence, non-synergetic and inconsistent implementation of the test method by the researchers to execute such simulations has been adopted, which inevitably results in unreliable findings. The review has made the first attempt to collect various facets of experimentally verified approaches for evaluating genoprotective compounds, as well as to acknowledge potential significance and constraints, and further focus on the assessment of end points which are required to validate such action. Henceforth, the review makes an incredible commitment by permitting readers to equate several components of their test arrangement with the provided simplified information, allowing the selection of convenient technique for the predefined compound from a central repository.

Burden of respiratory syncytial virus in adults in the United Kingdom: A systematic literature review and gap analysis.

Despite the growing recognition of a potentially significant respiratory syncytial virus (RSV) disease burden in adults, relevant evidence in the United Kingdom (UK) is limited. This systematic literature review (SLR) aimed to identify the disease burden of RSV in UK adults, including certain high-risk subgroups and existing evidence gaps. Published studies (2011 onwards) reporting epidemiological, economic and clinical burden outcomes in UK adults (≥15 years) with RSV were identified from indexed databases, including MEDLINE, Embase and the Cochrane library. High-risk groups included elderly (≥65 years), immunocompromised, co-morbid and co-infected patients. Outcomes included RSV incidence/prevalence, mortality, clinical presentation and direct/indirect resource use/costs. Twenty-eight publications on 28 unique studies were identified, mostly in general/respiratory indicator (n = 17), elderly (n = 10) and immunocompromised (n = 6) cohorts. Main outcomes reported in the general/respiratory indicator cohort were RSV infection incidence (seasonal/annual: 0.09-17.9%/6.6-15.1%), mortality (8,482 deaths/season) and direct resource use (including mean general practitioner [GP] episodes/season: 487,247). Seasonal/annual incidence was 14.6-26.5%/0.7-16% in high-risk cohorts. Attributed to RSV in the elderly were 7,915 deaths/season and 175,070 mean GP episodes/season. Only two studies reported on co-morbid cohorts. Clinical burden outcomes were only reported in general and immunocompromised patients, and no evidence was found in any cohort on indirect economic burden or RSV complications. Evidence captured suggests that RSV may have a substantial burden in UK adults. However, available data were limited and highly heterogenous, with further studies needed to characterise the burden of RSV in adults and to validate our findings.

DSCNet: Deep Skip Connections-Based Dense Network for ALL Diagnosis Using Peripheral Blood Smear Images.

Acute lymphoblastic leukemia (ALL) is a life-threatening hematological malignancy that requires early and accurate diagnosis for effective treatment. However, the manual diagnosis of ALL is time-consuming and can delay critical treatment decisions. To address this challenge, researchers have turned to advanced technologies such as deep learning (DL) models. These models leverage the power of artificial intelligence to analyze complex patterns and features in medical images and data, enabling faster and more accurate diagnosis of ALL. However, the existing DL-based ALL diagnosis suffers from various challenges, such as computational complexity, sensitivity to hyperparameters, and difficulties with noisy or low-quality input images. To address these issues, in this paper, we propose a novel Deep Skip Connections-Based Dense Network (DSCNet) tailored for ALL diagnosis using peripheral blood smear images. The DSCNet architecture integrates skip connections, custom image filtering, Kullback-Leibler (KL) divergence loss, and dropout regularization to enhance its performance and generalization abilities. DSCNet leverages skip connections to address the vanishing gradient problem and capture long-range dependencies, while custom image filtering enhances relevant features in the input data. KL divergence loss serves as the optimization objective, enabling accurate predictions. Dropout regularization is employed to prevent overfitting during training, promoting robust feature representations. The experiments conducted on an augmented dataset for ALL highlight the effectiveness of DSCNet. The proposed DSCNet outperforms competing methods, showcasing significant enhancements in accuracy, sensitivity, specificity, F-score, and area under the curve (AUC), achieving increases of 1.25%, 1.32%, 1.12%, 1.24%, and 1.23%, respectively. The proposed approach demonstrates the potential of DSCNet as an effective tool for early and accurate ALL diagnosis, with potential applications in clinical settings to improve patient outcomes and advance leukemia detection research.

Amelioration of cyclophosphamide-induced DNA damage, oxidative stress, and hepato- and neurotoxicity by Piper longum extract in rats: The role of γH2AX and 8-OHdG.

Background: The identification of genoprotectants is a promising strategy for improving human health. Piper longum has drawn scientific attention because of its diverse biological effects and traditional utilization. The current investigation aims to evaluate the genome-stabilizing potential of Piper longum against cyclophosphamide-associated genotoxicity. Methods: We adopted a funnel screening with a three-tier evaluation approach, where Piper longum was investigated in an acellular medium, peripheral blood lymphocytes, and a rodent model. The genoprotective action of the Piper longum extract was initially performed with plasmid pBluescript SK(-) DNA. Furthermore, the extract and various fractions were screened against cyclophosphamide-induced genotoxicity using a cytokinesis-block micronucleus assay and a chromosomal aberration assay in human peripheral blood lymphocytes. The genome-stabilizing action of the extract and potent (hexane) fraction was further confirmed in vivo in Wistar albino rats by evaluating them using mammalian erythrocyte micronucleus tests, DNA fragmentation, oxidative stress markers, 8-hydroxy-2-deoxyguanosine (8-OHdG), γH2AX, and histopathological lesions in the liver and hippocampus. Additionally, acute and sub-acute toxicity studies were conducted following the Organization for Economic Co-operation and Development (OECD) guidelines for rats. Furthermore, the extract was quantified and characterized by high-performance thin-layer chromatography (HPTLC), ultra-high performance liquid chromatography-mass spectroscopy (UPLC-MS), and gas chromatography-mass spectrometry (GC-MS). Results: The Piper longum ethanol extract was shown to protect plasmid pBluescript SK(-) DNA against H2O2-induced strand breaks. In human lymphocytes, the extract and hexane fraction showed a reduction in micronucleus formation (p < 0.001) and chromosomal aberrations (p < 0.01) against cyclophosphamide. Furthermore, the extract and fraction treatment, when administered at 200 mg/kg for 28 days in Wistar rats, restored cyclophosphamide-induced genomic instability by reducing micronucleus formation and DNA fragmentation; restoring redox homeostasis; decreasing 8-OHdG, a hallmark of oxidative DNA damage; reducing γH2AX, a DNA double-strand break (DSB) marker; and preserving the liver and hippocampus against histopathological lesions. The extract and fraction revealed no signs of systemic toxicity at the used doses. Piperine and piperlongumine are the major alkaloids quantified along with the presence of flavonoids in the ethanol extract and the presence of fatty acids and terpenoids in the hexane fraction of Piper longum. Conclusion: Our investigation confirms the genoprotective action of Piper longum by reducing cyclophosphamide-associated cytogenotoxicity, oxidative stress, hepato- and neurotoxicity, oxidative DNA damage, and DNA double-strand breaks. The outcomes are critical for mitigating the genotoxic effects of chemotherapy recipients, requiring further attention.

Altered hallmarks of DNA double-strand breaks, oxidative DNA damage and cytogenotoxicity by piperlongumine in hippocampus and hepatocytes of rats intoxicated with cyclophosphamide.

AIM: Cyclophosphamide is an effective anti-tumor agent, however, it induces genomic instability and tissue toxicity in clinical application. This study aims to evaluate the action of piperlongumine against cyclophosphamide-induced toxicity. MAIN METHODS: The action was investigated in rodent model of genomic instability, where piperlongumine (50 mg/kg) was orally co-administered with cyclophosphamide (5 mg/kg) for 28 days to Wistar albino rats. Further, piperlongumine was also examined for acute and sub-acute toxicity. KEY FINDINGS: Piperlongumine significantly reversed genotoxicity in high-proliferation tissue (bone marrow: p < 0.05) as well as in vital tissues (hippocampus: p < 0.01 and hepatocytes: p < 0.05), calculated as micronuclei formation and %DNA fragmentation. It also restored the redox homeostasis, counteracted the formation of oxidative DNA damage product and DNA double-strand break in vital tissues, indicated by reduction of 8-OHdG and γH2AX. TUNEL assay revealed that piperlongumine diminished the cyclophosphamide-associated apoptotic cell death in hippocampus as well as in liver tissue and conferred cytoprotection to the host. These findings were finally corroborated with the histopathological findings, where piperlongumine treatment restored the cellular viability of liver and hippocampus. Further, piperlongumine did not produce any toxic effects to rats in systemic toxicity studies. SIGNIFICANCE: Piperlongumine possesses genome stabilizing effect and reduces cyclophosphamide-associated DNA damage, oxidative stress, hepato-, and neurotoxicity, diminishes the DNA damage response pathway in the rat model, at the same time, conserves the micro-architectural details of liver and hippocampus. The findings are significant in terms of reducing genotoxic impact of chemotherapy-receiving patients.

Diverse Physiological Roles of Flavonoids in Plant Environmental Stress Responses and Tolerance.

Flavonoids are characterized as the low molecular weight polyphenolic compounds universally distributed in planta. They are a chemically varied group of secondary metabolites with a broad range of biological activity. The increasing amount of evidence has demonstrated the various physiological functions of flavonoids in stress response. In this paper, we provide a brief introduction to flavonoids' biochemistry and biosynthesis. Then, we review the recent findings on the alternation of flavonoid content under different stress conditions to come up with an overall picture of the mechanism of involvement of flavonoids in plants' response to various abiotic stresses. The participation of flavonoids in antioxidant systems, flavonoid-mediated response to different abiotic stresses, the involvement of flavonoids in stress signaling networks, and the physiological response of plants under stress conditions are discussed in this review. Moreover, molecular and genetic approaches to tailoring flavonoid biosynthesis and regulation under abiotic stress are addressed in this review.

Effect of the MAGL/FAAH Dual Inhibitor JZL-195 on Streptozotocin-Induced Alzheimer's Disease-like Sporadic Dementia in Mice with an Emphasis on Aß, HSP-70, Neuroinflammation, and Oxidative Stress.

Alzheimer's disease is identified by pathological hallmarks such as intracellular neurofibrillary tangles (NFTs) and extracellular amyloid ß plaques. Several hypotheses exist to define the neurodegeneration including microglial activation associated with neuroinflammatory processes. Recently, pharmacological inhibition of endocannabinoid (eCB)-degrading enzymes, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), is being investigated to modulate the pathology of Alzheimer's disease. While MAGL inhibitors upregulate 2-acyl glycerol (2-AG) levels and reduce neuroinflammation, FAAH inhibitors elevate anandamide (AEA) levels and prevent the degradation of HSP-70, thereby preventing the phosphorylation of tau protein and formation of NFTs in neural cells. We investigated the possible neuroprotective potential of the dual MAGL/FAAH inhibitor JZL-195 (20 mg/kg) against ICV-STZ-induced sporadic Alzheimer's disease (SAD) in Swiss albino mice using donepezil (5 mg/kg) as the standard. The protective effects of JZL-195 were observed by the reversal of altered levels of Aß1-42, HSP-70, neuroinflammatory cytokines, and oxidative stress markers. However, JZL-195 expressed no cognitive improvement when assessed by spontaneous alternation behavior and Morris water maze tests and no effects on the AChE enzyme level in the hippocampal tissues of mice. Therefore, the findings of the present study indicate that although JZL-195 exhibited no improvement in cognitive deficits associated with sporadic Alzheimer's disease, it displayed significant reversal of the biochemical anomalies, thereby suggesting its therapeutic potential against the sporadic Alzheimer's disease model.

Decrypting the interaction pattern of Piperlongumine with calf thymus DNA and dodecamer d(CGCGAATTCGCG)2 B-DNA: Biophysical and molecular docking analysis.

The mechanisms of interaction of DNA with pharmacological molecules are critical to understanding their therapeutic actions on physiological systems. Piperlongumine is widely studied for its anticancer potential. Multi-spectrometry, calorimetry and in silico studies were employed to study the interaction of piperlongumine and calf thymus DNA. UV-Vis spectroscopy illustrated a hyperchromic pattern in spectra of the calf thymus DNA-piperlongumine complex, while fluorescent quenching was observed in emission spectral studies. Competitive displacement assay demonstrated higher displacement and binding constant for DNA-rhodamine B complex by piperlongumine than DNA-methylene blue complex. Differential scanning calorimetry presented non-significant changes in melting temperature and molecular docking presented the precise interaction site of piperlongumine with calf thymus DNA at minor groove. Further, piperlongumine treatment did not result in pBluescript KS plasmid DNA cleavage as revealed from the DNA topology assay. All these experiments confirmed the binding of piperlongumine with DNA through minor groove binding mode.

Endogenous indole-3-acetic acid and nitric oxide are required for calcium-mediated alleviation of copper oxide nanoparticles toxicity in wheat seedlings.

The action of nanoparticles is increasingly being studied in recent years to minimize their toxic impacts. Besides this, efforts are also being made to minimize their toxicity in crop plants by using various chemicals, i.e. nutrients, donors of signaling molecules, plant hormones, and so on. However, associated alleviatory mechanisms are still not well known. Therefore, in the present study, we have investigated the toxicity of CuONPs and its mitigation by exogenously applied calcium (Ca). The focus was on whether indole-3-acetic acid (IAA) or endogenous nitric oxide (NO) has any role in accomplishing this task. CuONPs declined wheat growth due to increased accumulation of Cu and oxidative stress markers such as superoxide radicals, hydrogen peroxide, and lipid peroxidation (malondialdehyde) and it was also accompanied by a decline in endogenous NO. CuONPs also altered the redox status of ascorbate and glutathione by inhibiting the activity of their regenerating enzymes. This collectively leads to cell death in wheat seedlings. However, exogenous supplementation of Ca mitigated toxic effects of CuONPs by reducing the excess accumulation of Cu, which caused remarkable enhancement in growth, protein contents, photosynthetic pigments, and endogenous NO; altogether protecting wheat roots from cell death. Interestingly, addition of 2,3,5-triiodobenzoic acid (TIBA) further increased CuONPs toxicity even in the presence of Ca, but the addition of IAA rescued this effect of TIBA. These results clearly show that Ca mitigates CuONPs toxicity in wheat seedlings by involving IAA. Further, the results also showed that endogenous NO has a positive and indispensable role in Ca-mediated mitigation of CuONPs toxicity in wheat seedlings.

Aluminum toxicity and aluminum stress-induced physiological tolerance responses in higher plants.

Aluminum (Al) precipitates in acidic soils having a pH < 5.5, in the form of conjugated organic and inorganic ions. Al-containing minerals solubilized in the soil solution cause several negative impacts in plants when taken up along with other nutrients. Moreover, a micromolar concentration of Al present in the soil is enough to induce several irreversible toxicity symptoms such as the rapid and transient over-generation of reactive oxygen species (ROS) such as superoxide anion (O2•-), hydrogen peroxide (H2O2), and hydroxyl radical (•OH), resulting in oxidative bursts. In addition, significant reductions in water and nutrient uptake occur which imposes severe stress in the plants. However, some plants have developed Al-tolerance by stimulating the secretion of organic acids like citrate, malate, and oxalate, from plant roots. Genes responsible for encoding such organic acids, play a critical role in Al tolerance. Several transporters involved in Al resistance mechanisms are members of the Aluminum-activated Malate Transporter (ALMT), Multidrug and Toxic compound Extrusion (MATE), ATP-Binding Cassette (ABC), Natural resistance-associated macrophage protein (Nramp), and aquaporin gene families. Therefore, in the present review, the discussion of the global extension and probable cause of Al in the environment and mechanisms of Al toxicity in plants are followed by detailed emphasis on tolerance mechanisms. We have also identified and categorized the important transporters that secrete organic acids and outlined their role in Al stress tolerance mechanisms in crop plants. The information provided here will be helpful for efficient exploration of the available knowledge to develop Al tolerant crop varieties.

A comparative study of the effective response of di-potassium phosphate (K2HPO4) on physiological, biochemical and anatomical aspects of crops dwelling with zinc oxide nanoparticles toxicity.

The dipotassium phosphate (K2HPO4) is a source of phosphorus (P), which is an essential micronutrient for plant growth and reproduction and also acts as a stress alleviator against abiotic stresses. Therefore, it could also become a potential mineral to cope up with zinc oxide nanoparticles' (ZnONPs) toxicity in crops. This study primarily includes synthesis, characterization and differential toxic impacts of ZnONPs on two crop plantsThis study includes synthesis, characterization and differential toxic impacts of ZnONPs on two crop plants, i.e. Triticum aestivum and Solanum lycopersicum, as well as assuage the toxic impacts of ZnONPs through nutrient management approach implied via supplementation of P. The growth and physiological changes under toxic doses of ZnONPs and ameliorative potential of P in crop plants were examined by analysing growth, intracellular Zn accumulation, photosynthetic pigment contents, the kinetics of photosystem II (PS II) photochemistry, root cell anatomy and cell viability via histochemical staining 4',6-diamidino-2-phenylindole and propidium iodide. ZnONPs at 500 and 1000 µM concentrations significantly affected the growth, photosynthetic pigment and PS II photochemistry and cell death in both the plants. It also caused deformation in root anatomy of T. aestivum and S. lycopersicum. Whereas supplementation of P caused significant improvement against ZnONPs stress by causing remarkable enhancement in growth, photosynthetic pigments and activity of PS II photochemistry and decreased cell death. Moreover, the study also discloses the tolerant nature of S. lycopersicum comparing with T. aestivum seedlings. Thus, P is comparatively more effective in managing the ZnONPs toxicity in S. lycopersicum than in T. aestivum.

Metaheuristic-based Deep COVID-19 Screening Model from Chest X-Ray Images.

COVID-19 has affected the whole world drastically. A huge number of people have lost their lives due to this pandemic. Early detection of COVID-19 infection is helpful for treatment and quarantine. Therefore, many researchers have designed a deep learning model for the early diagnosis of COVID-19-infected patients. However, deep learning models suffer from overfitting and hyperparameter-tuning issues. To overcome these issues, in this paper, a metaheuristic-based deep COVID-19 screening model is proposed for X-ray images. The modified AlexNet architecture is used for feature extraction and classification of the input images. Strength Pareto evolutionary algorithm-II (SPEA-II) is used to tune the hyperparameters of modified AlexNet. The proposed model is tested on a four-class (i.e., COVID-19, tuberculosis, pneumonia, or healthy) dataset. Finally, the comparisons are drawn among the existing and the proposed models.

Histochemical Techniques in Plant Science: More Than Meets the Eye.

Histochemistry is an essential analytical tool interfacing extensively with plant science. The literature is indeed constellated with examples showing its use to decipher specific physiological and developmental processes, as well as to study plant cell structures. Plant cell structures are translucent unless they are stained. Histochemistry allows the identification and localization, at the cellular level, of biomolecules and organelles in different types of cells and tissues, based on the use of specific staining reactions and imaging. Histochemical techniques are also widely used for the in vivo localization of promoters in specific tissues, as well as to identify specific cell wall components such as lignin and polysaccharides. Histochemistry also enables the study of plant reactions to environmental constraints, e.g. the production of reactive oxygen species (ROS) can be traced by applying histochemical staining techniques. The possibility of detecting ROS and localizing them at the cellular level is vital in establishing the mechanisms involved in the sensitivity and tolerance to different stress conditions in plants. This review comprehensively highlights the additional value of histochemistry as a complementary technique to high-throughput approaches for the study of the plant response to environmental constraints. Moreover, here we have provided an extensive survey of the available plant histochemical staining methods used for the localization of metals, minerals, secondary metabolites, cell wall components, and the detection of ROS production in plant cells. The use of recent technological advances like CRISPR/Cas9-based genome-editing for histological application is also addressed. This review also surveys the available literature data on histochemical techniques used to study the response of plants to abiotic stresses and to identify the effects at the tissue and cell levels.

Structural modifications of plant organs and tissues by metals and metalloids in the environment: A review.

At the dawn of the industrial revolution, the exorbitant use of heavy metals and toxic elements by mankind unfurls a powerful and complex web of hazard all around the world that significantly contributed to unprecedented trends in environmental degradation. Plants as sessile organisms, that cannot escape from the stress directly, have adapted to this environment via concurrent configurations of several traits. Among them the anatomy has been identified as much more advanced field of research that brought the explosion of interest among the expertise and its prodigious importance in stress physiology is unavoidable. In conjunction with various other disciplines, like physiology, biochemistry, genomics and metabolomics, the plant anatomy provides a large data sets that are paving the way towards a comprehensive and holistic understanding of plant growth, development, defense and productivity under heavy metal and toxic element stress. Present paper advances our recent knowledge about structural alterations of plant tissues induced by metals and metalloids, like antimony (Sb), arsenic (As), aluminium (Al), copper (Cu), cadmium (Cd), chromium (Cr), lead (Pb), manganese (Mn), mercury (Hg), nickel (Ni) and zinc (Zn) and points on essential role of plant anatomy and its understanding for plant growth and development in changing environment. Understanding of anatomical adaptations of various plant organs and tissues to heavy metals and metalloids could greatly contribute to integral and modern approach for investigation of plants in changing environmental conditions. These findings are necessary for understanding of the whole spectra of physiological and biochemical reactions in plants and to maintain the crop productivity worldwide. Moreover, our holistic perception regarding the processes underlying the plant responses to metal(loids) at anatomical level are needed for improving crop management and breeding techniques.

A systematic review on Piper longum L.: Bridging traditional knowledge and pharmacological evidence for future translational research.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper longum, commonly referred as 'Pippali', has found its traditional use in India, Malaysia, Singapore and other South Asian countries as an analgesic, carminative, anti-diarrhoeic, immunostimulant, post childbirth to check postpartum hemorrhage and to treat asthma, insomnia, dementia, epilepsy, diabetes, rheumatoid arthritis, asthma, spleen disorder, puerperal fever, leprosy etc. AIM OF THE REVIEW: This review offers essential data focusing on the traditional use, phytochemistry and pharmacological profile of Piper longum thereby identifying research gaps and future opportunities for investigation on this plant. MATERIALS AND METHODS: This systematic survey was accomplished as per the PRISMA guidelines. The information was collected from books, and electronic search (PubMed, Science Direct, Lilca and Scielo) during 1967-2019. RESULTS: Many phytochemicals have been identified till date, including alkaloids as its major secondary metabolites (piperine and piperlongumine), essential oil, flavonoids and steroids. These exhibit a wide range of activities including anti-inflammatory, analgesic, anti-oxidant, anti-microbial, anti-cancer, anti-parkinsonian, anti-stress, nootropic, anti-epileptic, anti-hyperglycemic, hepatoprotective, anti-hyperlipidemic, anti-platelet, anti-angiogenic, immunomodulatory, anti-arthritic, anti-ulcer, anti-asthmatic, anthelmintic action, anti-amebic, anti-fungal, mosquito larvicidal and anti-snake venom. CONCLUSION: Amongst various activities, bioscientific clarification in relation to its ethnopharmacological perspective has been evidenced mainly for anti-amebic, anthelminthic, anti-tumor and anti-diabetic activity. However, despite traditional claims, insufficient scientific validation for the treatment of insomnia, dementia, epilepsy, rheumatoid arthritis, asthma, spleen disorder, puerperal fever and leprosy, necessitate future investigations in this direction. It is also essential and critical to generate toxicological data and pharmacokinetics on human subjects so as to confirm its conceivable bio-active components in the body.

Regulation of cadmium toxicity in roots of tomato by indole acetic acid with special emphasis on reactive oxygen species production and their scavenging.

Toxic impact of cadmium (Cd) on plants is well known which affects their productivity. To mitigate toxic impact of metals such as Cd, exogenous application of phytohormones like indole acetic acid (IAA) has been well recognized in the recent past. But, mechanisms related to the IAA-mediated mitigation of metal toxicity remain elusive. Therefore, in this study, effect of IAA on growth and photosynthetic attributes, nitric oxide, cell viability, reactive oxygen species (ROS) and ascorbate-glutathione cycle (AsA-GSH cycle) was investigated in tomato roots exposed to Cd stress. Cd declined growth and photosynthetic attributes which were accompanied by the excess accumulation of Cd and decreased level of nitric oxide (NO). Among photosynthetic attributes, quantum yield parameters were more sensitive to Cd and these results were in parallel of photosynthetic pigments. However, exogenously applied IAA together with Cd significantly improved level of NO, growth and photosynthetic attributes together with reduced accumulation of Cd. Cd enhanced level of superoxide radical and hydrogen peroxide leading to severe damage to lipids and membranes as indicated by increased level of lipid peroxidation and electrolyte leakage which collectively reduced cell viability of roots. Moreover, components of the AsA-GSH cycle i.e. enzymes (ascorbate peroxidase, monodehydroascorbate reducatse, dehydroascorbate reducatse and glutathione reductase) and metabolites (ascorbate and glutathione) were declined by the Cd. However, addition of IAA with Cd had up-regulated components of the AsA-GSH cycle. Interestingly, application of 2,4,6-triiodobenzoic acid (TIBA, a polar auxin transport inhibitor) diminished growth attributes and its combination with Cd worsened its toxicity and these events were in parallel with decline in NO content and enhancement in Cd accumulation. The results also showed that IAA was also able in mitigating Cd toxicity in tomato roots even in the presence of TIBA. Overall results show the essentiality of IAA in mitigating Cd stress in tomato roots through NO that up-regulates components of the AsA-GSH cycle for balancing ROS and their associated damages and hence much improved growth and photosynthetic attributes were noticed.

Preventive potentials of piperlongumine and a Piper longum extract against stress responses and pain.

AIM: To compare stress resistance increasing and analgesic activities of piperlongumine and a methanolic Piper longum fruit extract (PLE). METHODS: Efficacies of a single and repeated daily oral doses (1-256 mg/kg/day) of PLE, piperlongumine, and 50 mg/kg/day doxycycline against foot shock stress triggered alteration in body weights and core temperatures, and of their 11 daily doses on antidepressants like activity in tail suspension test and on pentobarbital induced sedation in male mice were compared. In another experiment, analgesic activities of single and repeated daily 5 mg/kg oral doses of piperlongumine and PLE in mice hot plate test and in acetic acid induced writing tests were compared with those of aspirin and doxycycline. RESULTS: After their single oral doses no effects of piperlongumine or PLE or doxycycline were observed in the footshock stress induced hyperthermia test or in hot plate test. However, significant effects of piperlongumine and PLE in both the tests were observed after their 5 or more daily doses. Both of them also dose dependently suppressed daily handling and repetitive testing triggered alterations in body weights and core temperatures. Their doxycycline like antidepressant activity in tail suspension test and aspirin like analgesic effects in acetic acid writhing test were observed after their 11 daily 5 mg/kg oral dose. CONCLUSION: Piperlongumine is another bioactive secondary metabolite of P. longum and other plants of piper species with stress response suppressing, analgesic, and anti-inflammatory activities. Its bactericidal activities can also contribute to its therapeutically interesting bio-activity profile.

Long lasting preventive effects of piperlongumine and a Piper longum extract against stress triggered pathologies in mice.

AIM: To compare doxycycline (DOX) such as oral efficacies of piperlongumine (PL) and a Piper longum fruits extract (PLE) as stress resistance inducers. MATERIALS AND METHODS: Efficacies of oral pretreatments with 5 mg/kg PL or PLE or of 50 mg/kg DOX for 10 consecutive days against stress resistance were compared. Mice in treated groups were subjected to a stress induced hyperthermia on the 1(st), 5(th), 7(th), and 10(th)day. Treated mice were then subjected to tail suspension test on the 11(th)day. Alteration in body weights, core temperatures, and gastric ulcers triggered by occasional exposures to foot shocks were determined. RESULTS: DOX like long-lasting protective effects of PL and PLE against gradual alterations in body weights, basal temperatures and transient hyperthermic responses triggered by foot shocks during the post-treatment days were observed. Altered responses of stressed mice in tail suspension test observed 1 day after the last foot-shock exposures and gastric ulcers and other pathologies quantified 1 day after the test were also suppressed in PL or PLE or DOX pretreated groups. CONCLUSION: PL and crude PLE are DOX like long-acting desensitizers of stress triggered co-morbidities. Reported observations add further experimental evidences justifying traditionally known medicinal uses of P. longum and other plants of the Piperaceae family, and reveal that PL is also another very long acting and orally active inducer of stress resistance. Efforts to confirm stress preventive potentials of low dose plant-derived products enriched in PL or piperine like amide alkaloids in volunteers and patients can be warranted.